April 2024

Forty-four per cent: reading the nausea figure properly

Trial adverse-event tables count episodes reported to a study nurse. They are the best data we have and they systematically…

Reflux, early satiety, and the volume the stomach will accept

A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.

Non-responders, and the honest state of the evidence about them

Receptor pharmacology is strong on average effects and almost silent on individual variation. That gap is where most reader…

A missed dose, modelled: what happens to retatrutide concentrations over the following fortnight

An accumulation model, drawn from published parameters, with its assumptions stated.

A schedule that bends does not break

Every major phase 3 protocol in this class allowed escalation to be delayed for tolerability. Almost no product label explains…

GIP was a failed target for thirty years. Then it was not.

A dual agonist is one molecule with two receptor activities. A co-formulation is two molecules in one pen. The coverage treats…

Why your endoscopist wants to know about your injection

This is the single interaction with ordinary medical care that patients most need to disclose, and it is the one most often not…

Blind duplicates: what happens when a laboratory does not know it is being watched

Duplicate submissions under different names test within-laboratory repeatability, which is a different quantity from…

A document, not a test: what a certificate actually is

Nothing on this page is difficult. It is simply unfamiliar, and unfamiliarity is what makes a weak certificate look like a…

Retest date, expiry date, and the two conventions being confused

A document is only as good as the chain that connects it to the material, and most chains here are two or three links longer…

Four ways a peptide comes apart

We describe each pathway in enough chemical detail to explain why it is invisible to the method the trade uses, because that is…

Why a dead-clean sterile filter can pass pyrogen straight through

Bacterial endotoxin is a heat-stable lipopolysaccharide from the outer membrane of Gram-negative organisms. It survives…

What the sequence tells you about how a peptide will fail

The sequence predicts the failure mode. A methionine predicts oxidation; an asparagine followed by a glycine predicts…

Asparagine, glycine, and the two residues that decide a shelf life

An isoaspartate rearrangement changes the molecule and not the mass. A method that confirms identity by molecular weight alone…

SURPASS-3 was built to answer the stopping question, and it did

Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are…

What the upper limit of normal for ALT should be, and why it is not

Asymptomatic pancreatic enzyme elevation is common on treatment and is not pancreatitis. The distinction is clinical, not…

Every fortnight, every third week, seasonally: an unstudied practice

What the exposure arithmetic says about a fortnightly schedule, and where the arithmetic stops being informative.

What happens when the drug is taken away: three randomised answers

The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately…

What STEP 3 measured, and what it was never powered to detect

What was pre-specified, what was exploratory, and what was calculated afterwards by people who did not run the trial.

Thiamine and the vomiting patient

Which markers are informative, which are confounded, and which move for reasons unrelated to nutrition.

What the upper limit of normal for ALT should be, and why it is not

Estimated glomerular filtration rate is a calculation with muscle mass in the denominator of its assumptions. In this population…

Grams per kilogram of what? The denominator problem in protein guidance

The practical difficulty is not knowing the target. It is meeting it on an appetite that has been pharmacologically reduced by…

Manual reintegration is legitimate, and it should be declared

We work through a single chromatogram twice, under two integration conventions, and show where the difference comes from.

Six words a verification badge would need to mean anything

A badge asserts that something was tested. It does not assert what, when, on whose sample, by what method, or whether the lot on…

What the paperwork is for, and who it was designed to protect

The header identifies the batch, the table records the tests, and the footer says who is answerable. Two of the three are…

Freezing a reconstituted vial: the ice-water interface problem

At low concentrations a measurable fraction of peptide can adsorb to glass and plastic surfaces, and the loss is largest exactly…

The number at the bottom of the certificate

A purity percentage is the most quoted figure in the research-peptide trade and one of the least examined. We asked four…

A document, not a test: what a certificate actually is

The purity figure is the least informative line on a well-constructed certificate and the only line most buyers read.

How a release document is put together in a regulated plant

Nothing on this page is difficult. It is simply unfamiliar, and unfamiliarity is what makes a weak certificate look like a…

Matrix, laser, needle: the plumbing that determines what you see

A brief and unromantic tour of the interface between a liquid sample and a vacuum.

Same material, different gradients, different answers

The Journal submitted split samples from single lots to three assay services, under names unconnected to this publication, and…

What the placebo arms of the withdrawal trials actually tell us

The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately…

Why people actually stop, in the order they actually stop

Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.

Why "muscle-sparing" is a marketing term and not a measurement

The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.

Vitamin D, adiposity, and a volume-of-distribution problem

Micronutrient guidance for this drug class is borrowed almost entirely from post-bariatric surveillance, where the anatomy is…

The mechanism behind the mechanism

A single drug producing both constipation and diarrhoea looks contradictory until the motility data is read properly.

Sarcopenia is a diagnosis, not a synonym for losing lean mass

The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.

The advice is mostly reasonable. The certainty is not earned.

Grading six widely repeated claims against the studies actually behind them.

Side effects, cost, supply, target: four reasons with four trajectories

Why the reason for stopping changes what happens afterwards.

We split six vials four ways and posted them

Duplicate submissions under different names test within-laboratory repeatability, which is a different quantity from…

The withdrawal trials, read as designs rather than warnings

The evidence on stopping is better than the evidence on almost anything else in this field, because somebody deliberately…

Same material, different gradients, different answers

Duplicate submissions under different names test within-laboratory repeatability, which is a different quantity from…

The submitted sample: the weakest link in the whole system

Every third-party report in this market describes a sample somebody chose to send. That choice is outside the laboratory’s…

Why people actually stop, in the order they actually stop

Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.

The supply gap as a clinical event

Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.

A tested vial is evidence about a vial

Every third-party report in this market describes a sample somebody chose to send. That choice is outside the laboratory’s…

Why the customs shed is the least documented step in this trade

Degradation rates rise exponentially with temperature while an arithmetic mean adds linearly. Mean kinetic temperature is the…

What we asked twenty suppliers about stability data

We asked twenty companies three questions about stability data and print every answer, refusal and non-response.

Falling ferritin is not always falling iron

A substantial proportion of the abnormal results generated during rapid weight loss are consequences of the weight loss rather…

Twenty-eight days is a number from somebody else’s product

We set out what is known, what is inferred and what is simply assumed about the fortnight after a vial is opened.

Why the bone question is harder than the muscle question

What the Journal would want measured before treating this as settled in either direction.

The three-times-upper-limit convention, and where it came from

Asymptomatic pancreatic enzyme elevation is common on treatment and is not pancreatitis. The distinction is clinical, not…

Equal area is not equal mass: the response factor problem

Peptide bonds absorb strongly near 214 nm; aromatic side chains absorb near 280 nm. A method reading at 280 is blind to any…

The isotope pattern tells you the charge, and the charge tells you the mass

A peptide has a monoisotopic mass and an average mass, they differ by several daltons at this molecular size, and a certificate…

Residual stomach content on endoscopy: the studies

A drug that delays gastric emptying complicates the assumption behind every fasting instruction in perioperative medicine. The…

The incidence tables, read line by line

Trial adverse-event tables count episodes reported to a study nurse. They are the best data we have and they systematically…

Dual, triple, co-formulated: a taxonomy the coverage keeps collapsing

Head-to-head data exists for some of these comparisons and not for others. This piece says which.

The one place the insulin literature and this class agree completely

Repeated injection into the same small area produces lipohypertrophy — thickened, rubbery subcutaneous tissue with blunted and…

GIP was a failed target for thirty years. Then it was not.

What adding GIP activity does, on the current evidence, and what remains unresolved.

Tolerability is the ceiling, and the ceiling is personal

The ceiling varies severalfold between people, and nothing measurable at baseline predicts where it sits.